Quaternary ammonium germicide compositions



Patented Jan. l2, 1954 QUATERNARY AMMONIUM GERMICIDE COMPOSITIONS Richard D. Stayner, Albany, Calif., assigner to California ResearchgCorporation, San Francisco, Calif., a corporation of Delaware Application September 5, 1950, Serial No. 183,278`

compositions which comprise a Quaternary ammonium germicide and a promoter.

Prior to my invention, Quarternary ammonium compounds, per se, have been used as germicides, etc. The activity of these compounds varies 'Widely with the different types of organic cation radicals contained therein. As a consequence, a great amount of experimental eiort and ex- 'pense has been necessary to develop more eicient types of materials. Such Quaternary ammonium 'compounds are usually costly and, in many cases, are characterized by poor eiciency in the control of microorganisms, .particularly spore-forming bacteria, fungi, molds, and the like.

It is an object of my invention to provide novel Quaternary ammonium compositions which are economical to produce and more eiicient than the Quaternary ammonium compounds themselves as germicides, particularly toward spore-forming bacteria, fungi, molds, and the like.

Other objects and advantages of my invention vWill be apparent from the disclosure which hereinafter appears.

I have found that a Quaternary ammonium germicide and pine oil may be combined in such proportions as to produce strongly germicidal -compositions having germicidal activity exceeding that of the Quaternary ammonium compounds themselves. This resultant improvement in eili- `ciency is highly unexpected since pine oil is of itself a relatively poor germicide, particularly toward spore-forming bacteria, fungi, etc., against vwhich even Quaternaries are relatively ineffective.

The production of these novel and more highly eiective germicidal compositions according to my Iinvention requires only the simplest of procedures. It involves none of the complicated experimentation that is necessary when improve- .ment of the germicidal eiiiciency of a Quaternary ammonium compound is attempted through modification of the hydrophobic cationic portion of -the molecule.

The extraordinary eiect of my discovery is -illustrated graphically by the curve shown in the accompanying drawing. Upon reference to this curve, it will be seen that when certain substantial amounts of a Quaternary ammonium compound are combined with pine oil, the resultant composition possesses germicidal activity against a representative fungus such as T. rosaceum far in excess of the Quaternary alone. On the other 3 Claims. (Cl. 167-25) eide compositions of my invention are prepared xcontaining a total of no more than about ,more fully illustrated in lgermicide and the `of pinevoil just sufficient to hand, when only small amounts such as about 5% of Quaternary ammonium compounds are added to pine oil as would customarily be done to improve the low germicidal eiliciency of the pine oil and to impart surface-active properties to it, just a moderate increase in the overall germicidal activity above that of pine oil alone is obtained.` This is only as expected since the germicidal activity of the Quaternary is recogniz ably stronger than that of the pine oil. The

terms germicide and germicidal as contemplated herein refer to that class of agents which destroys microorganisms-such as bacteria, fungi, algae, protozoa, etc., as well as the effect.

The Quaternary ammonium germicides used in the compostions of my invention can be any of several various types which fall Within the generic term. These compounds vare generally characterized by the formula wherein at least one of the radicals R1, R2, R3 and R4 attached to nitrogen atom is a hydrophobic aliphatic, unsaturated aliphatic, cycloaliphatic,

araliphatic or aliphaticaryl radical of from6 to -26 carbon atoms.

The hydrophobic radicals, more specifically, may be long-chain alkyl, longchain alkoxyaryl, long-chain alkylaryl, halogen substituted long-chain alkylaryl, long-chain alkylphenoxyalkyl, arylalkyl, etc., in nature. 'I'he remaining radicals on the nitrogen atom other than the preceding hydrophobic radicals may be substituents of hydrocarbon structure ordinarily 12 carbon atoms. Various compounds of these types are the disclosure which follows. Mixtures of the different Quaternaries may be used in my compositions as Well as the single compounds.

The proportions of the Quaternary ammonium pine oil are critical to my invent1on. However, these critical proportions may vary over a Wide range from a minimum amount promote the germicidal activity of the Quaternary ammonium compound up to a maximum amount of about 70%.

A Very marked improvement is obtained with proportions of Dine oil ranging from about 10` to about while compositions containing pine oil 1n proportions of about 20 to about 50% exhibit the greatest increase in germicidal activity.

The improved Quaternary ammonium germi- 3 by adding pine oil to the Quaternary ammonium compounds in suitable proportions and mixing them together. Various means for mixing and handling the materials will be obvious to persons skilled in the art from this disclosure and, as such, are contemplated by my invention.

As more specific examples of the diiferent types of Quaternary ammonium germicides in the novel compositions according to my invention as well as various compounds included in them, I can use the alkyl ammonium halides, such as` cetyl trimethyl ammonium bromide, doctadecyl dimethyl ammonium chloride, etc.; the alkyl aryl ammonium halides, as illustrated by octadecyl dimethyl benzyl ammonium chloride; N-alkylfv pyridinium halides, such as N-laurylpyri'dir'iium chloride; Quaternary ammonium salts containing ether linkages in the molecule, such as paratertiary octylphenoxyethoxyethyl dimethyl benzyl ammonium chloride; Quaternary ammonium compounds having oxygen in thev form of amide or` ester linkagesy as illustrated by N- (laurylcolaminoformylmethyl)epyridinum chloride; quaternary ammonillrll` Compounds containing a sulfonamide group, such as- 2phenyl.3,-.p-sulfami do-,phenylf-.undecyltetrazolium chloride.; aswell as Quaternary ammonium germicidescharacterized by a substituted aromatic nucleus such as lauryloxyphenyl trimetloyl ammonium chloride, dodecylbenzyl trimethyl ammoniuml chloride, chlorinated dodecylbenzyl trimethyl* ammonium chloride, dodeeylphenyl. trimethyl ammonium methosulfate, and the like.

Although any; of the.l above types. of; Quaternary ammoniumvgermicide is ordinarily satisfactory in my. novel compositions, those. which are particularly eiiective are the long-chain alkyl dimethyl benzyl. Quaternary. ammonium Salts. the alkyl.- phenoxyalkoxyalkyl dimethyl, benzylI Quaternary ammonium salts, the N-(acylcolaminoformylmethyl) -pyridinum salts, the long-chain alkyl trimethyl ammonium salts, as Well as the longchain alkylarylmethyl Quaternary ammonium compounds.

The long-chainV alkylarylmethyl Quaternary ammonium germicidesv which are. particularly adapted to the novel compositions of my. invenftionbelong tothe, class of Quaternary ammonium salts characterizer by the type formula is hydrogen or a methyl radical, m isfrom 1- to 4,

Yfis a hydrogen or a halogen, n is from 1 to8, R2,

lltaand R4 are substitutents of hydrocarbon structure containinga maximum total of l-2- carbon atoms, and X is a salt-forming anionic radical Which may be the same as Y.

In. the above alkylarylmethyl Quaternary ammonium germicides the long-chain alkyl radical R1 can beany alkyl group of from Sto 18 carbon atoms. When the alkyl radicals are of a straight chain nature, those containing as fewY as 8 to V10 carbon atoms arefoundv to be veryV satisfactory, but when branched chain structures predominate in the acyclic radical, the. most rsatisfactory groups arethose containing from 10 to 181 carbon atoms. Suitable alkyl radicals can be obtained from various sources such as the long-chain olefins of 8 to 18 carbon atoms derived from cracked. olefin-icpetroleum fractions or from Fischer-Tropsch synthesis. A. preferred source of 4 long acyclic alkyl radicals is the class of acyclic propylene polymers having from 9 to 15 carbon atoms per molecule, With those having from 12 to l5 carbon atoms being still more preferred.

The aryl nuclei of the long-chain alkylarylmethyl Quaternary germicides represented by the above formulae can be benzene, toluene, xylene, naphthalene, anthracene. etc., with benzene and toluene being preferred.

The N-substituted alkyl radicals of the longchainl alkylarylmethyl Quaternary ammonium compounds of this invention as already stated should contain no more than l2 carbon atoms, and preferably from. 3 to 10 carbon atoms. The hydrocarbon substitutents may be separate alkyl radicals attached to the nitrogen atom or they may be combined alkyl and cycloalphatic hydrocarbon substituents as in the case of N-ethyl piperidine. The hydrocarbon substituents also may be a single aromatic ring occupying all three of the nitrogen valences as illustrated in the; case of pyridine.

Since thev cationic portion of the. Quaternary ammonium germicides; contemplated in this` invention. is considered the active, component, the salt-forming anionic radical X is. not. generally regarded as beingv critical in nature. Any @Bionic radicalsl capable of yielding water-soluble. salts can be used. Examples of such anionic. radicals` are the, halidesy sulfates, phosphates, carbonatos, nitrite, alkyl sulphates, alkyl phosphates, formate, acetate,l tartrate, and the. like. Haliclev radicals. such as chloride andv bromidev are. particu.- larly suitable with the chloride being preferred. Where the aniom'c. portion of the Quaternary am.- monium germicide molecule. is anY alkyl sulfate,

short-chain alkyl sulfates, in particular, are. contemplated, such as` methylsulfate, ethylsulfate, propylsulfate, etc.

The compounds can be prepared in several, different ways, all. of which will beapparent to. one skilledin the art. fromv my disclosure. For exam.-

vple, the long-chain` alkylarylmethyl Quaternary ammonium germicides can be suitably prepared by chloromethylation; of a, long-chain alkylaryl compound toproduce an alkylarylmethyl chloride which can then be condensed with any suit;- abletertiary. amine, to. give the desired1 product. Halogenatedlong-chain alkylarylrmethyl. quaternary ammonium compounds, on the other hand are conveniently prepared by.' direct halogenation of along-chain alkylaryl. compound having from l; to 4 methyl radicalsl attached; to the. aryl nu,- cleus. When the halogenation isY carried out in theA absence of any; halogenation` catalyst: which might promoteY substitution of the rings, a. prod;- uctA isderived containing halogen. in. the,i longchain. alkyl radical as well asin oneof'the; methyl radicals substituted onV the aryl. nucleus. This compound. which may be denominated a. halogenated alkylarylmethyl chloride can thenbe confdensed with any suitable tertiaryv amine asin the precedingV example to give the desired halogenatedA long-chain alkylarylmethyl Quaternary ammonium compound'.

Examples of the preferred long-chain alkylarvlrr'iethylV Quaternary ammonium germicides coming Within the scope of the above `formula according to my invention are: octylbenzyl trimethyl ammonium` chloride, nonylnaphthyl tri;- methyll ammonium chloride, dodecylbenzyl pyridinium chloride, dodecylbenzyl trimethyl ammonium bromide, dodecylmethylbenzyl tri-1 methyl ammoniumy chloride, cetylbenzyl triffm'ethyl ammonium methosulfate, octylbi-phenyl'- .Specification 51D6. dilution, the greater the germicidal power of the -composition tested.

triethyl ammonium nitrate, octadecylbenzyl trimethyl ammonium chloride, and the like.

'I'he pine oil utilized in the long-chain alkylaryl quaternary ammonium germicide and pine oil compositions according to my invention is available in a number of different forms. It has been defined as being an oil obtained by steam distillation of the oleoresin from Pinus palustris Miller and certain other species of pine (Merck Index, 5th Ed., 1940). Pine oil as it is contemplated herein usually boils above about G-220 C. and has a specific gravity of about 0.9. Although it is sometimes used as a disinfectant by itself, it has only mild germicidal properties as illustrated by its maximum effective dilution against T. rosaceum of about 1:30 compared to 1:80 for phenol.

Various mixtures of quaternary ammonium germicides and pine oil were prepared for testing to illustrate the proportional limits within which L the germicidal activity of the quaternary ammonium germicide and pine oil composition exceeds that of both the pine oil and the Quaternary ammonium compound. Such mixtures were prepared by placing the quaternary v ammonium germicide in a vessel and adding pine oil, following which the ingredients were intimately mixed to produce the new and greatly improved germicidal compositions of this invention. The emcacy of the different compositions 5 Fungicidal activity of Quaternary ammonium germicide and pine oil compositions toward Trichophyton rosaceum Proportions, Percent by Weight gig Quaternary Ammonium Killing Compound Tested Dihmo Quater' Pi e ou in Ware? nary n Dodecylbenzyl Trimethyl Am monium Chloride 0 100 1:30

28. 6 71. 4 1:1000 33.3 66. 7 1:1330 40.0 60. O 1:1600 52. 2 47. 8 1:2630 59. 3 40. 7 1:2060 63.5 36. 5 1:3080 68. 6 31.4 1:3463 73. 5 26. 5 1:3340 89.8 10. 2 1 :1800 Do 1 100 0 1:1500 Lauryl Dimethy Benzy Ammonium Chloride 50 1:1500 Chlorinated Dodecylbenzyl trimethyl ammonium chloride (approx. 5 chlorine atoms) 11.0 89.0 1:430 Do 12. 4 87.6 1:50() Do 16.7 83.3 1:667 Do 100 0 1:500

The values for germicidal activity set out in the above table were obtained by determining the maximum eiective killing dilution when mixed with water of different compositions prepared according to this invention as well as of the pure Quaternary ammonium germicide and pine oil ingredients. The maximum effective dilution illustrates the killing power of the different compositions against a representative fungus such as Trichophyton rosaceum and was obtained by the testing method set out in Navy Department The higher the effective From the above table of results and reference :to the curve in the accompanying drawing which was obtained by plotting the maximum effective dilution against the` various proportions of quaternary and pine oil, the unexpectedly high germicidal activity of compositions according'to my invention is readily apparent. It can be seen that my germicidal compositions containing substantial proportions of Quaternary ammonium germicides and less than about '70% by weight of pine oil are decidedly superior to either pine oil or the Quaternary ammonium compound in germicidal enciency. 'Furthermore any lowering of germicidal activity which would ordinarily be expected when a strongly germicidal material is diluted with a very mild germicide such as pine oil is surprisingly absent when the proportions according to the teaching of my invention are utilized.

Because of their higher germicidal activity, my novel compositions are more efflcaciousl than either quaternary ammonium germicides or pine oil alone as well as compositions of pine oil fortied with only a small amount of quaternary ammonium germicide. Their greater efticacy renders them extraordinarily useful in the control of microorganisms, particularly spore-forming bacteria, fungi, and the like. Such uses include the disinfection of utensils and equipment used in drinking, eating and the preparation of foods, etc. Wearing apparel, bedding, upholstery, and the like, can also be eiectively sterilized by the use of my germicidal compositions. Floors, walls, as well as various equipment such as lavatories, toilets, etc. in areas where it is desirable to promote germ-free surroundings can be conveniently disinfected with these germicidal compositions because of their greater germicidal activity. Other applications such as their use as antiseptic ingredients in germicidal detergents, ointments, cosmetics, etc. are also indicated.

The germicidal compositions, according to my invention, may contain various dyes or coloring agents which are compatible with the quaternary ammonium germicide and the pine oil in order to improve the general appearance of the compositions. The use of various perfumes and odormasking agents is also contemplated.

In some instances, the germicidal compositions of this invention may contain water as, for example, when a composition is prepared by adding pine oil to an aqueous solution of the quaternary ammonium germicide. In the presence of certain amounts of water as, for example, amounts exceeding about 30% and less than about 90% by Weight of the aqueous quaternary ammonium germicide and pine oil solution, a separation of the pine oil and aqueous quaternary ammonium germicide mixture may occur. Although such separation has no effect on the germicidal activity of my compositions, it will be preferred to maintain the Water in amounts of less than about 30% and more than about 90% by weight whenever clear and completely miscible or homogeneous mixtures are desired for the sake of appearances.

The foregoing description and examples of the germicidal compositions according to my invention are intended as illustrative only. Many obvious variations and modifications of the invention will be apparent to those skilled in the art. All such variations and modifications as come within the scope of the appended claims are contemplated by my invention.

I claim:

1. A germicidal composition which comprises from @i0 to 90% fby weight of .an N-alkyibenzyl- '.N,N,r -`trialkyl quaternary ammonium chloride and from l'l to 60% by 'weight .of lpine loil, said alkyl group :on the benzyl nucleus containing 4-roms to 1`f8carbon1atomsnndsaid nitrogen alkyl substituents 4containing no 'more "than n total `of '1"2 carbonatoms.

If2. A germicida'l Icomposition which comprises 'f'ro'm vl40 to '90% Eby VvWeiggf'l: of 'an Nialk-ylbenzyl- ,N,N-tr`ialkyl Quaternary ammonium chloride and from l0 to 60% by weight of 'pine-oil, said alkyl groupon tlieb'enzyl lnucleusbeing a propyl- -ene 'polymer containing from 12 "to l5 carbon atoms and'sa'id nitrogen alkyl substituents Vcon taining n'o more than a -total of '12 carbon atoms.

v3'. -A germcidal composition which comprises 10 to 60% by Weight of pine oil and 40 lto 90% by 'weight of Adodecyl vbenzyl ltrimethyl ammonium Achloriiie.

RICHARD D. STAYNER.

VErnulsions z 8 References Cited 1in the le of this patent' UNITED STATES PATENTS Number Y Name Date 2,372,159 ,Manchey etal Mar. 2Q, 19.45 2,383,775 Cvraig'et .a-l Aug. 28, 1.945

`OTHER REFERENCES Lawrence et al.: Journal American VPharmaceutical Association, November 1941, volume 36, `pages VV353 1:01358.

Rawlins et al.: Journal American 'Pharmaiceutical Association, volume 32 '(1943), lpages '111 to '16.

-Shippen et al.: U. .S. iD. A. Bulletin No. '9'8'9 entitled, Pine-Oil and Pine Distillate 'Product Method of "Production, 'Chemical Properties, andDisinfectantAction, October 7, 1921, pages 1,130 16. 

1. A GERMICIDAL COMPOSITION WHICH COMPRISES FROM 40 TO 90% BY WEIGHT OF AN N-ALKYLBENZYLN,N,N-TRIALKYL QUATERNARY AMMONIUM CHLORIDE AND FROM 10 TO 60% BY WEIGHT OF PINE OIL, SAID ALKYL GROUP ON THE BENZYL NUCLEUS CONTAINING FROM 8 TO 18 CARBON ATOMS AND SAID NITROGEN ALKYL SUBSTITUENTS CONTAINING NO MORE THAN A TOTAL OF 12 CARBON ATOMS 